oxytocin and Sepsis

Sepsis is a potentially life-threatening systemic inflammatory syndrome characterized by dysregulated host immunological responses to infection. Uncontrolled immune cell activation and exponential elevation in circulating cytokines can lead to sepsis, septic shock, multiple organ dysfunction syndrome, and death. Sepsis is associated with high re-hospitalization and recovery may be incomplete, with long term sequelae including post-sepsis syndrome. Consequently, sepsis continues to be a leading cause of morbidity and mortality across the world. In our recent review of human chorionic gonadotropin (hCG), we noted that its major properties including promotion of fertility, parturition, and lactation were described over a century ago. By contrast, the anti-inflammatory properties of this hormone have been recognized only more recently. Vasopressin, a hormone best known for its anti-diuretic effect, also has anti-inflammatory actions. Surprisingly, vasopressin's close cousin, oxytocin, has broader and more potent anti-inflammatory effects than vasopressin and a larger number of pre-clinical studies supporting its potential role in limiting sepsis-associated organ damage. This review explores possible links between oxytocin and related octapeptide hormones and sepsis-related modulation of pro-inflammatory and anti-inflammatory activities.

Topics: Anti-Inflammatory Agents; Female; Humans; Oxytocin; Peptide Hormones; Sepsis; Vasopressins

Although the role of oxytocin in the pathophysiology of sepsis is still unknown, rising preclinical evidence suggests that oxytocin is possibly involved. However, no direct clinical studies have measured the levels of oxytocin during sepsis. In this preliminary study, the serum oxytocin levels were evaluated throughout the duration of sepsis.. Twenty-two male patients over 18 years of age with a SOFA score of 2 points or more who were admitted to the ICU were included. Patients with a history of neuroendocrine, psychiatric, and neurologic disorders, cancer, an infection caused by COVID-19, shock due to reasons other than sepsis, a history of psychiatric or neurologic medication use, and those who died during the study were excluded. The main endpoint included the measurement of serum oxytocin levels using radioimmunoassay at 6, 24, and 48 h of the ICU admission.. Mean serum oxytocin level was higher at 6 h of ICU admission (41.27 ± 13.14 ng/L) than after 24 and 48 h of ICU admission (22.63 ± 5.75 and 20.97 ± 7.61 ng/L respectively) (. Our study, while reporting increased serum oxytocin levels in the initial phase of sepsis and decline afterward, supports the possible contribution of oxytocin in the pathophysiology of sepsis. Given that oxytocin seems to modulate the innate immune system, future investigations are necessary to assess the potential role of oxytocin in the pathophysiology of sepsis.

Topics: Adolescent; Adult; COVID-19; Hospitalization; Humans; Immunity, Innate; Intensive Care Units; Male; Oxytocin; Prognosis; Retrospective Studies; Sepsis

Although several studies demonstrate the anti-inflammatory effect of oxytocin in different pathophysiological processes, there are limited data describing the impact of oxytocin on acute respiratory distress syndrome (ARDS). We aimed to elucidate the protective effect of oxytocin in ARDS with histopathological evaluation and radiological imaging in addition to biochemical markers.. Fecal intraperitoneal injection procedure (FIP) was performed on 24 of 32 rats included in the study for creating a sepsis model. Rats were randomly assigned into four groups: control group (no procedure was applied, n = 8), untreated septic group [was operated (FIP) and received no treatment, n = 8], placebo group (FIP, treated with 10 ml/kg of saline at once, n = 8), and treated group (FIP, treated with 0.1 mg/kg of oxytocin at once, n = 8). Chest CT was performed for all rats 20 hours after the procedure and density of the lungs were measured manually by using HU. All animals were sacrificed for histopathological examination of lung damage and blood samples were collected for biochemical analysis.. Plasma malondialdehyde (MDA), lactic acid (LA), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL 1-β) levels were significantly increased in the placebo (FIP + saline) and the untreated (FIP) groups, and plasma levels of all biomarkers were reversed by oxytocin. Further, the density of the lung parenchyma (Hounsfield unit) on CT images and the histopathological lung damage score values were closer to the control group in the oxytocin-treated group compared to the placebo group.. Our findings suggested that oxytocin could exert anti-inflammatory, antioxidant and protective effects in FIP-induced ARDS.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Lung; Oxytocin; Rats; Sepsis; Tomography, X-Ray Computed; Tumor Necrosis Factor-alpha

Sepsis promotes an inflammatory state in the central nervous system (CNS) that may cause autonomic, cognitive, and endocrine changes. Microglia, a resident immune cell of the CNS, is activated in several brain regions during sepsis, suggesting its participation in the central alterations observed in this disease. In this study, we aimed to investigate the role of microglial activation in the neuroendocrine system functions during systemic inflammation. Wistar rats received an intracerebroventricular injection of the microglial activation inhibitor minocycline (100 μg/animal), shortly before sepsis induction by cecal ligation and puncture. At 6 and 24 h after surgery, hormonal parameters, central and peripheral inflammation, and markers of apoptosis and synaptic function in the hypothalamus were analyzed. The administration of minocycline decreased the production of inflammatory mediators and the expression of cell death markers, especially in the late phase of sepsis (24 h). With respect to the endocrine parameters, microglial inhibition caused a decrease in oxytocin and an increase in corticosterone and vasopressin plasma levels in the early phase of sepsis (6 h), while in the late phase, we observed decreased oxytocin and increased ACTH and corticosterone levels compared to septic animals that did not receive minocycline. Prolactin levels were not affected by minocycline administration. The results indicate that microglial activation differentially modulates the secretion of several hormones and that this process is associated with inflammatory mediators produced both centrally and peripherally.

Topics: Animals; Brain; Corticosterone; Disease Models, Animal; Male; Microglia; Minocycline; Neurons; Neurosecretory Systems; Oxytocin; Rats; Rats, Wistar; Sepsis; Vasopressins

Acute lung injury (ALI) is one of the leading causes of death in sepsis. Endothelial inflammation and dysfunction play a prominent role in development of ALI. Glycolysis is the predominant bioenergetic pathway for endothelial cells (ECs). However, the role of EC glycolysis in ALI of sepsis remains unclear. Here we show that both the expression and activity of PFKFB3, a key glycolytic activator, were markedly increased in lipopolysaccharide (LPS)-treated human pulmonary arterial ECs (HPAECs) in vitro and in lung ECs of mice challenged with LPS in vivo. PFKFB3 knockdown significantly reduced LPS-enhanced glycolysis in HPAECs. Compared with LPS-challenged wild-type mice, endothelial-specific Pfkfb3 knockout (Pfkfb3

Topics: Acute Lung Injury; Animals; Disease Models, Animal; Endothelial Cells; Endothelium, Vascular; Endotoxemia; Glycolysis; Humans; Inflammation; Intercellular Adhesion Molecule-1; Lipopolysaccharides; Lung; Mice; Monocytes; NF-kappa B; Oxytocin; Phosphofructokinase-2; Pulmonary Edema; Sepsis; Signal Transduction; Vascular Cell Adhesion Molecule-1

Sepsis is known to affect neuroendocrine circuits: injections of lipopolysaccaride are potent stimulators of oxytocin secretion from the posterior lobe, acute sepsis leads to uterus contractions and spontaneous abort. Here, we report changes in expression and distribution of hypothalamic oxytocin in rats that had been subjected to caecal ligation and puncture which led to acute sepsis. Septic animals showed loss of oxytocin immunostaining in perikarya of the supraoptic and paraventricular nuclei and an increase of oxytocin positive fibres, suggesting a shift of oxytocin pools into the axonal compartment. Immunostaining of the posterior lobe revealed reduction of oxytocin in septic rats. Magnocellular neurons in supraoptic- and to a lesser extent in paraventricular nuclei showed nuclear immunoreactivity for the protooncogene c-Fos, indicating stimulation of transcriptional activity upon sepsis. Contrary to magnocellular oxytocin immunoreactivity, we observed increased oxytocin immunoreactivity in cell bodies and processes of periventricular nucleus and in perivascular neurons. Oxytocin neurons in other regions of the hypothalamus and the preoptic region did not appear to be affected by acute sepsis. Our findings suggest a differential activation of neurohypophyseal and cerebrospinal fluid contacting oxytocin systems while centrally projecting oxytocin neurons may not be affected. Systemic oxytocin levels may serve as additional diagnostic marker for sepsis.

Topics: Animals; Hypothalamus; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Sepsis

Oxytocin (OXT) secretion during cecal ligation puncture (CLP)-induced sepsis has not yet been examined. Although immune properties have been attributed to OXT, its effect on CLP-sensitized macrophages has never been investigated. We analyzed OXT secretion during CLP and its effect in CLP-sensitized macrophage cultures.. Male Wistar rats were decapitated 4, 6 or 24 h after CLP surgery or sham operation and blood, brain and neurohypophyses were collected for OXT measurements. In another set of animals we studied the effect of OXT on nitrite, tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-10 production of peritoneal macrophages harvested at 6 and 24 h after CLP.. In the early phase of sepsis (4-6 h), OXT levels increased in plasma and decreased in hypothalamus and neurohypophysis. In the late phase (24 h), plasma and neurohypophyseal levels remained basal. In the paraventricular, the OXT content remained low, but in the supraoptic increased. Macrophages of the early phase of sepsis pretreated with OXT and stimulated with lipopolysaccharide showed decreased nitrite, TNF-α and IL-1β levels, but no alteration in IL-10 production. In the late phase, they showed reduction only on IL-1β.. OXT secretion during sepsis may represent a neuroendocrine response contributing to the overall host response to infection by decreasing the proinflammatory response and oxidative stress.

Topics: Animals; Cytokines; Macrophages; Male; Nitric Oxide; Oxytocin; Radioimmunoassay; Rats; Rats, Wistar; Sepsis

Topics: Animals; Antioxidants; Male; Melatonin; Oxytocin; Polyneuropathies; Sepsis

Critical illness polyneuropathy is an acute neuromuscular disorder of critically ill patients and is characterized by limb and respiratory muscle weakness. The purpose of the study was to evaluate the neuroprotective effects of melatonin (MEL) and oxytocin (OT) on the early stage of sepsis by recording compound muscle action potentials and measuring plasma tumor necrosis factor (TNF)-α levels, lipid peroxidation (malondialdehyde; MDA), and total antioxidant capacity.. One hundred adult male Sprague-Dawley rats were included in the study. The cecal ligation and puncture (CLP) procedure was performed to induce the sepsis model. MEL (10, 20, and 40 mg/kg), OT (0.4, 0.8, and 1.6 mg/kg), and a combination of MEL (20 mg/kg) and OT (0.8 mg/kg) were administered intraperitoneally in the first hour of surgery. Electromyography (EMG) studies were achieved 24 h after CLP surgery and then blood samples were collected for biochemical measurements.. EMG findings revealed that compound muscle action potential amplitude was significantly decreased and distal latency was prolonged in the CLP group compared with the sham group (P < 0.05 and P < 0.0005). Moreover, the animals that received CLP surgery showed significantly higher TNF-α and MDA levels and lower total antioxidant capacity values than the sham group. The administration of MEL and OT to rats significantly abolished the EMG alterations and suppressed oxidative stress and TNF-α release in CLP-induced rats.. The inflammatory processes and imbalance in oxidative/antioxidative status play important roles in the pathogenesis of critical illness polyneuropathy. We suggest that both oxytocin and melatonin may have beneficial effects against sepsis-induced polyneuropathy in critical illness.

Topics: Animals; Antioxidants; Drug Evaluation, Preclinical; Electromyography; Lipid Peroxidation; Male; Malondialdehyde; Melatonin; Oxytocin; Polyneuropathies; Rats; Rats, Sprague-Dawley; Sepsis; Tumor Necrosis Factor-alpha

To determine the effect of conservative management of morbidly adherent placentae on maternal morbidity and mortality and to review management options. All case notes of patients with placenta accreta and percreta between June 2008 and August 2010 were studied retrospectively.. Eight placentae percretae and 4 placentae accretae were identified out of a total of 11,358 deliveries.All 12 patients underwent caesarean section. Placentae percretae were intentionally left in situ. Interventional radiology was used in these cases. There was one emergency hysterectomy for massive obstetric haemorrhage,one case of disseminated intravascular coagulation,one case of early sepsis and 3 cases of delayed sepsis.Average blood loss was 2490 ml with the mean volume transfused being 1425 ml. The mean hospital stay was 7 days and 2 patients were admitted to intensive care. One patient was readmitted with sepsis complicated by a utero-cutaneous fistula (complete placenta praevia).Another patient required re-embolisation 5 months post delivery for persistent haemorrhage. No ureteric or bladder injuries occurred.. Conservative management of placenta percreta is an alternative to caesarean hysterectomy. It is associated with lower maternal morbidity rates.However, monitoring for sepsis and secondary postpartum haemorrhage is essential. Rare complications such as utero-cutanus fistulae may occur.

Topics: Blood Loss, Surgical; Cesarean Section; Disseminated Intravascular Coagulation; Embolization, Therapeutic; Female; Humans; Hysterectomy; Oxytocics; Oxytocin; Placenta Accreta; Placenta, Retained; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications; Retrospective Studies; Sepsis; Treatment Outcome

Sepsis induces massive production of inflammatory mediators, such as nitric oxide (NO), and causes neuroendocrine and cardiovascular alterations. This study investigates the involvement of the central NO-cGMP pathway in arginine vasopressin (AVP) and oxytocin (OXY) gene expression during sepsis induced by cecal ligation and puncture (CLP). Male Wistar rats received an i.c.v. injection of ODQ (0.25 μg/μL), a selective inhibitor of the heme site of soluble guanylate cyclase, or of 1% dymethilsulfoxide (DMSO), as vehicle. Thirty minutes after the injections, sepsis was induced by cecal ligation and puncture or the animals were sham operated. The ODQ pre-treatment did not alter the progressive NO increase observed after CLP. In the supraoptic nucleus (SON), this pretreatment increased the relative gene expression ratio of AVP and OXY in the initial phase of sepsis, but in the late phase, the gene expression of both hormones was reduced. In the paraventricular nucleus (PVN), soluble guanylate cyclase inhibition caused an even larger decrease in the relative gene expression ratio of AVP and OXY during sepsis. These results are indicative of a role of the NO-cGMP pathway in hormonal synthesis in the SON and PVN of the hypothalamus during polymicrobial sepsis.

Topics: Animals; Arginine Vasopressin; Cyclic GMP; Enzyme Inhibitors; Gene Expression Regulation; Male; Nitric Oxide; Oxadiazoles; Oxytocin; Paraventricular Hypothalamic Nucleus; Quinoxalines; Rats; Rats, Wistar; Sepsis; Signal Transduction; Supraoptic Nucleus

Sepsis, commonly associated with enhanced generation of reactive oxygen metabolites, leads to multiple organ dysfunctions. The neurohypophyseal hormone oxytocin (OT), released during social contact, was recently shown to modulate the immune and inflammatory processes. We investigated the protective role of OT against sepsis-induced pelvic inflammation.. Under anesthesia, sepsis was induced in female Sprague-Dawley rats (200-250 g) by cecal ligation and perforation method. Sham-operated rats served as controls. Either saline or OT (1 mg/kg) was given subcutaneously immediately after and at the 16th hour, and rats were decapitated at the 24th hour of sepsis induction. Colon, uterus, and liver samples were obtained for the histopathological analysis of damage and for the measurement of myeloperoxidase (MPO) activity, indicating neutrophil infiltration, malondialdehyde (MDA), indicating lipid peroxidation, and glutathione (GSH), a key antioxidant, levels.. Colonic, uterine and liver MDA levels in the sepsis group were significantly increased (P < 0.01-P < 0.001), while colonic and uterine GSH levels were decreased (P < 0.05-P < 0.01) when compared to the control group. OT treatment reversed the MDA and GSH levels back to the control levels, while hepatic GSH levels were not altered. MPO activity in the colon and liver was increased by sepsis (P < 0.05-P < 0.001) while OT treatment abolished the elevated MPO activity. Collagen levels in the uterus and liver were increased by sepsis (P < 0.01) and OT treatment reduced the collagen levels in both tissues (P < 0.01-P < 0.05). Serum TNF-alpha levels were significantly increased by sepsis (P < 0.001) and OT treatment abolished the sepsis-induced increase in TNF-alpha levels.. OT protects against sepsis-induced oxidative damage by acting as an antioxidant agent and its protective effect in the colon and liver appears to be dependent on its inhibitory effect on neutrophil infiltration. Our results suggest that OT may have a therapeutic value in limiting sepsis-associated multiple organ damage.

Topics: Animals; Antioxidants; Collagen; Female; Glutathione; Malondialdehyde; Multiple Organ Failure; Neutrophils; Oxytocin; Peroxidase; Rats; Rats, Sprague-Dawley; Sepsis; Tumor Necrosis Factor-alpha

A case-control study was used to (1) examine the intrapartum characteristics of term neonates with early-onset group B streptococcal sepsis and (2) determine what percentage of patients meet The American College of Obstetricians and Gynecologists guideline for intrapartum administration of antibiotics.. Twenty-one women delivered of term neonates who contracted early-onset group B streptococcal sepsis were matched with 63 mothers who were colonized with group B streptococci. The women were matched for race, age, parity, and gestational age. A Student t test and chi2 analysis were performed. Significance was defined as p < 0.05.. The attack rate was 2.1 instances of sepsis per 1000 live births. For both groups, the maternal demographics and the actual birth weights were similar. Case mothers compared with controls had longer labor (11.4 +/- 6.9 vs 5.8 +/- 4.3 hours, p < 0.0001), had longer time elapsed between rupture of membranes and delivery (10.3 +/- 6.4 vs 3.2 +/- 3.6 hours, p < 0.0001); required oxytocin more often (76% vs 32%, p < 0.001); required more pelvic examinations (6 or more; 71% vs 46%, p < 0.05); and had a significantly higher cesarean section rate (33% vs 3%; p < 0.001). Only 10% (2 of 21) of case mothers met The American College of Obstetricians and Gynecologists guideline for chemoprophylaxis.. The American College of Obstetricians and Gynecologists guideline for chemoprophylaxis identifies only 10% of women whose term newborns contract early-onset group B streptococcal sepsis.

Topics: Adult; Anti-Bacterial Agents; Cesarean Section; Delivery, Obstetric; Extraembryonic Membranes; Female; Humans; Infant, Newborn; Labor, Obstetric; Male; Oxytocin; Pregnancy; Sepsis; Streptococcal Infections; Time Factors

Chorioamnionitis is an inflammatory reaction occurring in the fetal membranes of the placenta. It is usually associated with premature rupture of the membranes, whether spontaneous or artificial. Rupture of the fetal membranes sets off a time bomb that threatens both maternal and fetal welfare. The seriousness of this threat is dependent upon several variables: the length of gestation, economic status of the patient and the duration of the rupture. There is a controversy about the relative importance of these variables and about the proper degree of aggressiveness necessary to achieve optimum fetal salvage. When chorioamnionitis occurs, most obstetricians agree that the uterus should be evacuated by the most expeditious route. Usually oxytocic induction will accomplish delivery without difficulty, but should it fail to effect cervical ripening and dilatation within a reasonable time, cesarean section should be performed without further delay. If cesarean section is necessary in the presence of gross infection, hysterectomy is advocated by some.

Topics: Abortion, Therapeutic; Amnion; Chorion; Extraembryonic Membranes; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Inflammation; Labor, Induced; Oxytocin; Pregnancy; Pregnancy Complications; Sepsis

Topics: Abortion, Therapeutic; Female; Glucose; Humans; Hypernatremia; Hysterectomy; Oxytocin; Pregnancy; Prostaglandins; Sepsis; Sodium Chloride; Urea

Topics: Animals; Ergonovine; Female; Oxytocin; Pregnancy; Puerperal Infection; Sepsis; Swine; Swine Diseases

Topics: Abortion, Septic; Chloramphenicol; Female; Humans; Hydrocortisone; Metaraminol; Norepinephrine; Oxygen Inhalation Therapy; Oxytocin; Penicillins; Phenylephrine; Pregnancy; Sepsis; Shock; Shock, Septic; Streptomycin; Water-Electrolyte Balance